Details for Patent: 11,701,352

Which drugs does patent 11,701,352 protect, and when does it expire?

Patent 11,701,352 protects OPIPZA and is included in one NDA.

This patent has one patent family member in one country.

Summary for Patent: 11,701,352

Title:	Process for preparing aripiprazole oral soluble film
Abstract:	The present invention is directed to an aripiprazole oral soluble film and a preparation method thereof. The aripiprazole oral soluble film comprises 10-60% w/w of aripiprazole in a crystalline state and 30-95% w/w of one or more film-forming materials, wherein 90% of the aripiprazole particles have a size of ≤14.3 μm and are uniformly blended in the film without visible undispersed particles. The aripiprazole oral soluble film has excellent bioavailability, uniformity, stability, and palatability. The oral soluble film preparation is prepared by first grinding aripiprazole particles to have desired small particle sizes, then blending the aripiprazole particles with film forming materials in an aqueous solution to a uniform suspension, defoaming the suspension, and coating the suspension on a substrate and drying it to form a film.
Inventor(s):	Rongbin Ling, Lingyu Cai, Fuxiang LIN, Yong Yu, Xiaojin Xiao
Assignee:	Xiamen LP Pharmaceutical Co Ltd
Application Number:	US17/552,333
Patent Claim Types: see list of patent claims	Compound; Process;

US Patent 11,701,352: Aripiprazole Oral Soluble Film Claims, Scope and Patent Landscape

US Patent 11,701,352 is a process patent directed to manufacturing an aripiprazole oral soluble film. Its commercial significance depends on whether a competing manufacturer uses the claimed particle-size, crystalline-state, aqueous blending, defoaming and coating sequence. The patent does not claim aripiprazole itself, an oral film as a product, or every method of making an aripiprazole film.

The strongest infringement risk is concentrated in claim 1. Claims 2 through 8 add narrower milling, polymer, solvent, defoamer and vacuum-processing limitations. The principal design-around routes are to use amorphous aripiprazole, a particle-size distribution outside the claimed threshold, a nonaqueous process, a different mixing sequence, or a process that omits the required plate-and-frame blending step.

What does US Patent 11,701,352 cover?

The patent covers a manufacturing process for an aripiprazole oral soluble film in which aripiprazole remains crystalline during particle-size reduction and is incorporated into an aqueous film-forming suspension.

Claim 1 requires every one of the following limitations:

Claim element	Required technical condition
Dosage form	Aripiprazole oral soluble film
Active ingredient	Aripiprazole in a crystalline state
Particle processing	Milling until 90% of particles are smaller than 14.3 micrometers
Solid-state condition	Aripiprazole maintains its crystalline state during milling
Vehicle	Aqueous solution
Initial blending	Homogenization at a speed of at least 1,500 rpm
Secondary blending	Plate-and-frame blending
Suspension quality	Uniform suspension
Air removal	Defoaming
Film production	Coating on a substrate and drying

This is a process claim, not a composition claim. A film containing crystalline aripiprazole could fall outside claim 1 if it was made by a different process. Conversely, a manufacturer can face process infringement even if its final film has the same ingredients as a film made by a noninfringing process.

The claim uses sequential language. The process must proceed from milling, to homogenization, to plate-and-frame blending, to defoaming, and then coating and drying. Whether substantial compliance with that sequence is sufficient would depend on claim construction and the manufacturing evidence.

How narrow is claim 1?

Claim 1 is materially narrower than a general claim to an aripiprazole oral film. It contains several cumulative limitations that create both enforceability value and design-around opportunities.

Crystalline aripiprazole requirement

The claim requires aripiprazole to remain crystalline during milling. A process that intentionally converts the active ingredient into an amorphous form should fall outside the literal scope of this limitation.

The crystalline-state limitation may be tested using techniques such as powder X-ray diffraction, differential scanning calorimetry, solid-state nuclear magnetic resonance or related solid-state characterization. The relevant issue is not only whether the starting material is crystalline, but whether crystallinity is maintained after the claimed milling operation.

A process using partially amorphous material may create a factual dispute. The result would depend on how the claim defines “maintains a crystalline state,” the patent specification, prosecution history and the evidence concerning the material produced by the accused process.

Particle-size limitation

The phrase “90% of the aripiprazole particles have a size of <14.3 μm” is a distribution-based limitation. It is not equivalent to saying that the average particle size is below 14.3 μm.

The most likely technical interpretation is a D90 threshold, meaning that 90% of particles are below 14.3 μm. Particle-size measurements can vary depending on:

• laser diffraction or microscopy methodology;
• wet or dry dispersion;
• agglomerate treatment;
• refractive-index assumptions;
• sampling and batch homogeneity; and
• whether the measurement is taken before or after blending.

These variables are important in litigation. A process may appear compliant under one particle-size method and noncompliant under another. The patent holder would likely seek batch records, validated analytical methods, milling logs and retained-sample testing.

Required blending sequence

Claim 1 requires homogenization at a speed of at least 1,500 rpm followed by plate-and-frame blending. Both operations appear mandatory.

Potential noninfringing alternatives include:

• homogenization below 1,500 rpm;
• use of a planetary, rotor-stator, propeller or high-shear mixer without plate-and-frame blending;
• plate-and-frame blending before homogenization;
• simultaneous rather than sequential operations; or
• a process using only one validated mixing stage.

The strength of these alternatives depends on whether the accused equipment performs the same claimed functions under the doctrine of equivalents. A manufacturer that uses different equipment but replicates the same operating sequence and physical result may still face an equivalents argument.

What do claims 2 through 8 add?

Claim	Added limitation	Practical effect
2	Milling is bead milling, air crushing or colloid milling	Limits the milling technology
3	Bead milling has scatter axis speed above 3,000 rpm and more than three cycles	Narrows bead-milling embodiments
4	Film former is hypromellose, polyvinyl alcohol, copovidone, povidone, hydroxyethyl cellulose, hydroxypropyl cellulose or a combination	Defines a closed list of identified film-forming materials
5	Aqueous solution contains no organic solvent	Excludes solvent-containing aqueous systems
6	Aqueous solution further contains a defoamer	Requires defoamer in the blending medium
7	Defoamer includes dimethicone, simethicone, oleyl alcohol or a combination	Identifies specific defoamer embodiments
8	Defoaming is vacuum defoaming	Requires vacuum-based air removal

Claim 3 is particularly process-specific. “Scatter axis speed” appears to identify a machine operating parameter. Its scope may depend on how the specification defines the term and whether the accused equipment has a technically equivalent shaft, axis or rotor-speed parameter.

Claim 4 uses “selected from the group consisting of,” which normally creates a closed Markush group. A film-forming polymer outside the listed group should not literally satisfy this limitation, although claim 1 remains independent of claim 4 and does not require one of those polymers.

Claim 7 uses “comprises,” making it open-ended. A defoamer containing dimethicone, simethicone or oleyl alcohol could satisfy the claim even if other excipients are also present.

Claim 8 appears to contain a drafting error: “deforming” likely refers to “defoaming.” The dependency and technical context indicate vacuum defoaming as the intended limitation. The enforceability effect would depend on the issued patent text, prosecution record and any available correction or claim-construction ruling.

What formulations are protected by US 11,701,352?

The claims protect manufacturing embodiments using an aqueous film-forming system. The expressly identified polymers are:

• hypromellose;
• polyvinyl alcohol;
• copovidone;
• povidone;
• hydroxyethyl cellulose; and
• hydroxypropyl cellulose.

The claims do not specify a particular polymer concentration, aripiprazole loading, film thickness, plasticizer, sweetener, flavor, colorant, pH modifier, surfactant or disintegration agent.

Claim 1 also does not require any specific polymer. A process using a different film-forming material may still infringe claim 1 if all other limitations are met. It would not infringe claim 4 unless the material falls within the listed group.

Claim 5 creates a separate solvent-free embodiment. An aqueous system containing ethanol, acetone, isopropanol or another organic solvent should not satisfy claim 5, but it could still infringe claim 1 because claim 1 does not prohibit organic solvent.

Is this a product patent, formulation patent or method-of-use patent?

US 11,701,352 is best classified as a manufacturing-process patent with formulation-related limitations.

Patent category	Coverage under the supplied claims
Aripiprazole compound	No
Aripiprazole polymorph or solid form	No standalone composition claim
Oral soluble film product	No standalone product claim
Film formulation	Indirectly, through process limitations
Manufacturing process	Yes
Method of treating a disease	No
Dosing regimen	No
Packaging or device	No

The patent may be commercially relevant to an oral film product even without a product claim because manufacturing evidence can establish infringement. Its value is lower against a competitor that purchases or licenses finished film from a supplier using a noninfringing process.

When does US Patent 11,701,352 lose exclusivity?

The patent’s exact expiration date cannot be established from the claims supplied. US patent term generally runs 20 years from the earliest effective nonprovisional filing date, subject to terminal disclaimers, patent-term adjustment and any applicable patent-term extension under 35 U.S.C. §§ 154 and 156.

The issue date alone does not determine expiration. The controlling diligence items are:

1. earliest effective US or international priority date;
2. nonprovisional application filing date;
3. continuation, divisional or continuation-in-part status;
4. terminal disclaimer records;
5. patent-term adjustment;
6. patent-term extension; and
7. maintenance-fee status.

A process patent of this type normally does not receive Hatch-Waxman pediatric exclusivity merely because it concerns an approved active ingredient. Any exclusivity associated with aripiprazole products would be assessed separately from the patent term.

What is the Orange Book status of this patent?

A process patent is generally not the primary type of patent listed in the FDA Orange Book. Orange Book listing focuses on patents claiming an approved drug substance, drug product, or method of use submitted in connection with an approved application. FDA Orange Book guidance distinguishes these categories from manufacturing-process patents.[1]

US 11,701,352 should not be treated as an Orange Book barrier without confirmation that it has been submitted and accepted for listing against a specific approved drug application. The supplied claims do not identify an NDA, ANDA reference product, approved aripiprazole oral-film product or Orange Book listing.

Aripiprazole has FDA-approved products in several dosage forms, including tablets, orally disintegrating tablets, oral solution, injectable products and extended-release injectable suspensions. The existence of those approvals does not establish approval of the claimed oral soluble film or listing of this patent against any of them.[2]

What generic entry risks exist?

The risk profile differs between a conventional aripiprazole generic and an aripiprazole oral-film competitor.

Conventional tablets and oral solutions

A generic tablet or oral solution would generally not practice the claimed oral-film manufacturing process. US 11,701,352 therefore presents limited direct risk to conventional aripiprazole generic entry.

Oral soluble films

An oral-film competitor faces higher risk if it:

• uses crystalline aripiprazole;
• mills the active to a D90 below 14.3 μm;
• uses aqueous processing;
• homogenizes at 1,500 rpm or higher;
• follows with plate-and-frame blending;
• defoams; and
• coats and dries the suspension.

The risk is lower if the competitor documents a different crystalline or amorphous state, particle-size distribution, mixing sequence, vehicle, or coating process.

Generic launch scenarios

Scenario	Likely risk under the supplied claims
Tablet or oral solution	Low direct process-claim risk
Oral film using amorphous aripiprazole	Lower literal infringement risk
Oral film using crystalline aripiprazole with D90 above 14.3 μm	Lower risk, subject to measurement
Oral film using aqueous homogenization below 1,500 rpm	Lower risk
Oral film using homogenization but no plate-and-frame blending	Lower risk
Oral film using organic solvent	May avoid claim 5, but not necessarily claim 1
Oral film made outside the US and imported	Potential liability under 35 U.S.C. § 271(g) if the patented process materially changes the imported product
Film made by a contract manufacturer	Risk may extend to both manufacturer and parties inducing or contributing to infringement

How strong is the patent estate?

The supplied claims indicate a focused process estate rather than a broad platform estate.

Strengths

• Claim 1 combines measurable process conditions.
• The particle-size threshold provides a concrete infringement parameter.
• The crystalline-state requirement links milling to solid-state control.
• The claims cover a sequence that may be embedded in commercial manufacturing instructions.
• Dependent claims provide narrower fallback positions around common equipment and excipients.

Weaknesses

• No standalone product claim is supplied.
• No claim covers aripiprazole oral films made by every manufacturing route.
• Several limitations are easy to target through process changes.
• Particle-size testing may produce disputes over method and sampling.
• “Maintains a crystalline state” may require technical interpretation.
• The claim appears vulnerable to prior-art combinations involving micronization, aqueous film casting, high-shear mixing and vacuum defoaming.

Validity will likely turn on whether the prior art disclosed the combination of crystalline aripiprazole, the specific D90 threshold, the specified blending sequence and film-coating conditions. Under 35 U.S.C. § 103, the issue would be whether a skilled person would have had a reason to combine those features with a reasonable expectation of success.[3]

Are Paragraph IV challenges likely?

A Paragraph IV certification is available when an ANDA applicant asserts that a listed patent is invalid, unenforceable or will not be infringed. The practical relevance of Paragraph IV depends first on whether US 11,701,352 is listed in the Orange Book against the reference product and whether the ANDA seeks approval of a product that practices the claimed process.

If the patent is not Orange Book-listed, it would not ordinarily create a conventional Paragraph IV certification obligation. A competitor could still face ordinary patent litigation based on manufacturing conduct, including discovery into the process used to produce the ANDA product.

For an aripiprazole oral-film ANDA, a Paragraph IV strategy would likely focus on:

• noninfringement based on particle size;
• noninfringement based on amorphous rather than crystalline aripiprazole;
• omission of plate-and-frame blending;
• use of a different mixing speed or sequence;
• solvent-based processing;
• invalidity based on obviousness; and
• indefiniteness or enablement arguments concerning particle measurement and process terminology.

What patent litigation and settlements affect this patent?

No litigation, settlement or license information is established by the supplied claims. The patent number alone does not establish that the patent has been asserted, challenged, licensed or adjudicated.

A litigation review should distinguish among:

• district-court infringement actions;
• Patent Trial and Appeal Board inter partes review or post-grant review;
• ANDA litigation under the Hatch-Waxman framework;
• declaratory-judgment actions;
• foreign counterpart litigation; and
• license or settlement agreements.

Any settlement could impose launch restrictions, authorized-generic rights, manufacturing covenants or geographic limits that materially change the practical expiry date. Those commercial terms cannot be inferred from the claim language.

What geographic coverage does the patent provide?

US 11,701,352 provides US patent rights only. Foreign protection requires separate national or regional patents in the relevant jurisdictions. A US process patent can create exposure for:

• manufacturing in the United States;
• use of the claimed process in the United States;
• sale or importation of products made by the claimed process under 35 U.S.C. § 271(g); and
• inducement or contributory infringement tied to US activity.

The patent does not automatically block manufacture in Europe, India, China, Japan or other jurisdictions. Foreign family members must be reviewed separately for claim scope, status, term and prosecution amendments.

What manufacturing and IP barriers matter most?

The main manufacturing barrier is process reproducibility. Achieving a sub-14.3 μm D90 while preserving crystallinity can require controlled milling energy, temperature, residence time and solid-state monitoring. The subsequent aqueous suspension must remain uniform and processable without excessive foaming or sedimentation.

The principal IP diligence points are:

1. determine the actual D90 test method;
2. verify whether crystalline aripiprazole is required after milling or only in the starting material;
3. map homogenizer speed and equipment configuration;
4. confirm whether plate-and-frame blending is a discrete operation;
5. identify the defoaming equipment and operating conditions;
6. review the prosecution history for amendments and disclaimer statements;
7. identify continuations and divisionals;
8. check Orange Book records and FDA product approvals; and
9. compare each commercial batch record with the claim limitations.

Key Takeaways

• US 11,701,352 is a narrow, multi-step process patent for making aripiprazole oral soluble films.
• Claim 1 is the principal claim and requires crystalline aripiprazole, D90 below 14.3 μm, high-speed homogenization, plate-and-frame blending, defoaming, coating and drying.
• Claims 2 through 8 narrow the process by specifying milling technologies, bead-milling parameters, film-forming polymers, solvent restrictions and defoaming agents.
• The patent does not, based on the supplied claims, cover aripiprazole as a compound, every aripiprazole film, or a therapeutic method of use.
• Conventional aripiprazole tablets and oral solutions present limited direct risk under these claims.
• Oral-film competitors should prioritize design-arounds involving solid state, particle size, mixing sequence and equipment.
• The patent’s exact expiration date, Orange Book status, litigation history, licenses and settlement terms are not established by the claim text.
• Foreign protection cannot be assumed from the US patent.

FAQs

Can a competitor sell an aripiprazole oral film without infringing US 11,701,352?

Yes. A competitor may avoid literal infringement by using a nonclaimed solid state, particle-size distribution, mixing sequence, solvent system or film-manufacturing process, subject to the doctrine of equivalents.

Does using hypromellose automatically create infringement?

No. Hypromellose is a limitation of claim 4, not the entire patent. Infringement still requires the process limitations of claim 1 and the other limitations incorporated through dependency.

Does a particle size below 14.3 μm prove infringement?

No. The claim requires that 90% of particles be below 14.3 μm and that aripiprazole maintain its crystalline state. Both conditions, along with the remaining process steps, must be established.

Can a contract manufacturer be liable?

Potentially. A contract manufacturer that performs the claimed process may face direct infringement exposure, while a sponsor or customer may face inducement or contributory-infringement theories depending on its conduct and knowledge.[4]

Does FDA approval of an aripiprazole product prove patent infringement?

No. FDA approval addresses safety, effectiveness and regulatory requirements. It does not determine whether a manufacturer practices the steps of US 11,701,352 or whether the patent is valid and enforceable.

References

1. U.S. Food and Drug Administration. (2023). Approved drug products with therapeutic equivalence evaluations: Orange Book. https://www.fda.gov/drugs/drug-approvals-and-databases/approved-drug-products-therapeutic-equivalence-evaluations-orange-book

2. U.S. Food and Drug Administration. (n.d.). Aripiprazole drug approval information and labeling. https://www.accessdata.fda.gov/scripts/cder/daf/

3. United States Code. (2023). 35 U.S.C. §§ 103, 154, 156, 271. Office of the Law Revision Counsel. https://uscode.house.gov/

4. U.S. Patent and Trademark Office. (2024). Manual of Patent Examining Procedure, §§ 2111, 2131, 2133, 2181. https://www.uspto.gov/web/offices/pac/mpep/maker/index.htm

5. U.S. Patent and Trademark Office. (2023). United States Patent No. 11,701,352. Patent Center. https://patentcenter.uspto.gov/

Drugs Protected by US Patent 11,701,352

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Xiamen Lp Pharm Co	OPIPZA	aripiprazole	FILM;ORAL	216655-001	Jul 22, 2024		RX	Yes	No			Y
Xiamen Lp Pharm Co	OPIPZA	aripiprazole	FILM;ORAL	216655-002	Jul 22, 2024		RX	Yes	No			Y
Xiamen Lp Pharm Co	OPIPZA	aripiprazole	FILM;ORAL	216655-003	Jul 22, 2024		RX	Yes	Yes			Y

International Family Members for US Patent 11,701,352

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
China	111991373